The brightly colored images produced by a new $1 million microscope at Pacific Northwest National Laboratory are starting to provide answers about how human health might be affected by nanoparticles.
The multi-photon confocal microscope was just one item on the laboratory's wish list that its been able to purchase with $60 million of federal economic stimulus money awarded to PNNL's Environmental Molecular Sciences Laboratory, or EMSL.
EMSL had a five-year plan for purchasing scientific equipment, but the additional money allowed it to accelerate up to 80 percent of that plan, said Allison Campbell, EMSL director. That's a huge advantage, she said.
The power of EMSL is in integrating multiple sophisticated scientific instruments at the same location to solve the nation's most complex scientific problems. By purchasing them all at once instead of during half a decade, plans could be made to maximize that integration.
"It's going to help us really tackle the hard problems and advance the science more rapidly," Campbell said.
EMSL is a national user facility, playing host to researchers across the world who require its unique set of instruments and computational power to tackle difficult scientific challenges.
The 31 new instruments, systems and upgrades being purchased with the $60 million -- many of which include microscopy and mass spectrometry capabilities -- will help attract researchers at all levels. But they will be particularly important in attracting experienced and distinguished researchers, Campbell said.
Some of the instruments are purchased off the shelf, but about 40 percent were custom built by a vendor or by EMSL in a collaboration between machinists and scientists, she said.
The multi-photon confocal microscope will be used for a broad range of research focused on the study of living cells and tissue, including what happens when nanoparticles are introduced into an organism or their environment.
In one research project, the live lung cells from a mouse glow green and researchers can see that nanoparticles that glow red have been enclosed in the cells' vesicles, which can transport substances.
It's a possible clue to how nanoparticles someday might be used to deliver drugs in people.
In another research project, translucent embryonic fish are being watched under the microscope as they grow to see what happens to nanoparticles in the fish. It could provide clues to how nanoparticles may affect other vertebrates, including humans.
Joe Fisher, a doctoral student at Oregon State University working under the direction of professor Robert Tanguay, makes the drive to the Tri-Cities to put zebrafish in a culture dish sample under the new multi-photon confocal microscope by the time they're 24 hours old.
"The reason I come to EMSL -- the reason I drove five hours to get here -- is to use the microscope," Fisher said. "You can do this research with other microscopes but they are far more complicated, and you will get much less data."
The microscope combines three technologies -- nonlinear two-photon excitation, laser scanning confocal microscopy and Fluorescence Lifetime Imaging -- to create an image.
The technology allows the microscope to look deep into living tissue with less damage to live cells than older systems and can be used to reconstruct a three-dimensional image.
It also can detect 32 fluorescent colors, allowing researchers to tag proteins with different dye colors to see how they interact over time.
"It is cutting edge," said Galya Orr, an EMSL senior research scientist and capability lead.
In the Oregon State University research, the microscope acts as an incubator, keeping the embryonic fish alive as they are studied after nanoparticles are added to their water.
They are fully grown in about 120 hours, giving Fisher a five-day window from fertilization to take high-resolution time-lapse photos to record nanoparticles as they enter the samples and to track their progress throughout the zebrafish to gather toxicity data.
"These samples are still alive," he said in a statement. "For studying the entire three-dimensional shape and seeing the small particle amounts inside the zebrafish, you realize the power of this microscope."
Nanoparticles too small to be see by the naked eye show promise in solving problems ranging from pinpointing medical diagnoses to creating more durable materials.
But scientists have yet to determine exactly how nanoparticles may interact within the body when people are exposed to them, intentionally or unintentionally.
Research at this point, such as Orr's study of their activity in mouse lung cells, is so early that it's being done to understand basic principles.
"We cannot study every nanoparticle available so we are trying to deduce rules about what properties are good and which to stay away from," she said.
For instance, positively charged nanoparticles may not be as good for cells as those that are negatively charged on their surface, like cells are.
EMSL expects to have all its new scientific equipment delivered by the end of the year.